Osmotic blood-brain barrier disruption: pharmacodynamic studies in dogs and a clinical phase I trial in patients with malignant brain tumors.
Infusion of 25% mannitol in saline into the internal carotid artery of dogs disrupts the blood-brain barrier (BBB) in a controlled and reproducible manner (osmotic disruption), whereas mannitol infused through the common carotid artery produces variable disruption of the BBB. Compared to controls, infusion of methotrexate in dogs after osmotic disruption produced significantly higher drug levels in brain. We report very preliminary data on the effects of osmotic disruption with mannitol in five patients harboring malignant brain tumors.
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D004285:Dogs; D004341:Drug Evaluation; D007839:Functional Laterality; D006801:Humans; D007261:Infusions, Intra-Arterial; D007700:Kinetics; D008353:Mannitol / Q000008:administration & dosage* / Q000494:pharmacology; D008727:Methotrexate / Q000008:administration & dosage*; D009994:Osmolar Concentration
D008353:Mannitol; D008727:Methotrexate